Evaluation of Fomepizole and High-Dose N-Acetylcysteine Use for High-Risk Acetaminophen Overdose

Introduction: High-risk acetaminophen (APAP) ingestion causes glutathione depletion and subsequent hepatocellular injury from N-acetyl-p-benzoquinone imine (NAPQI) accumulation. Cincinnati Drug & Poison Information Center’s (DPIC) 2023 guidance recommends high-dose N-acetylcysteine (HD NAC) (400 mg/kg over 16 hours) with adjunctive fomepizole for patients meeting the following high-risk criteria: APAP levels >600 mcg/mL or correlated high-risk concentration thresholds on the Rumack-Matthew nomogram or APAP level multiplied by the highest LFT (AST or ALT) >10,000. This project aimed to describe institutional NAC and fomepizole prescribing practices post-guideline implementation.


Methods: This was a single-center, retrospective review of patients admitted to the University of Cincinnati Medical Center for concern of high-risk APAP toxicity. The primary outcome assessed compliance to high-risk APAP management guidelines, specifically use of fomepizole and NAC dosing patterns. Secondary outcomes included patient characteristics, ICU length of stay (LOS), APAP levels, and LFT trends.


Results: A total of 20 patients were reviewed who received adjunctive fomepizole for concern of APAP toxicity. Patients had a median age of 38 years (IQR 30-58 years), 7 (35%) were male, and 18 (90%) had detectable APAP levels on admission. ICU admission occurred in 10 (50%) patients with a median ICU LOS of 2.89 days (IQR 1.7-5.3 days). APAP levels on admission were 42.5 mcg/mL (IQR 21-64 mcg/mL), and peaked at 93 mcg/mL (IQR 33–198 mcg/mL). Peak AST and ALT were 5732 U/L (IQR 2948-8544 U/L) and 5460 U/L (IQR 2540-6955 U/L), and peak INR was 2.5 (IQR 1.4-6.4). Patients’ peak LFT×APAP level result was 28,030 (IQR 18,667–304,969). 17 (85%) patients were appropriately prescribed fomepizole for high-risk APAP toxicity, while only 2 (10%) patients received the appropriate HD NAC maintenance dose. Fomepizole was appropriately dosed at 15mg/kg for all patients.


Conclusions: Following the 2023 Cincinnati DPIC guidance update, fomepizole use was largely appropriate among high-risk patients, while NAC maintenance dosing was inconsistent with few patients receiving guideline-concordant dosing. These findings highlight the need for further guideline education and electronic medical record order set optimization for high-risk APAP ingestions.